Vitamin d3 double compounds



' Brockmann Patented Dec. 2, 1941 VITAMIN D3 DOUBLE COMPOUNDS Otto Linsert, wuppertal Elberield, Germany, assignor, by mesne assignments, to Alba Pharmaceutical Company. 1110., New York, N. Y., a corporation of New York.

' No Drawing. Application June 22, 1939, Serial No. 280,581. In Germany July 11, 1938 '3 Claims- (Cl. zoo-397.2)

This invention relates to vitamin D: double compounds.

It is known that 7-dehydrocholesterol is converted into an antirachitically highly active transformation product by chemically active irradiation, particularly by ultraviolet irradiation. The transformation product which has been prepared in pure form has been called vitamin D3. (Zeitschrift fiir Physiologische Chemie 256, 1938, page 252) has proved that the vitamin D occurring in nature, for instance in halibut or tunny liver oils, is for the most part identical with the vitamin D3.

The vitamin D3, immaterial whether produced from natural sources or by irradiation of 7-dehydrocholesterol, shows the disadvantage that it is sensitive to oxygen. n storage without special precautions the vitamin D3 in pure form as well as in preparations, for instance solutions or mixtures of inert ingredients, is changed and therefore the antirachitic efllcacy is gradually decreased.

In accordance with the present invention it has been found that the vitamin D3 forms double compounds with sterols of the group consisting of cholesterol, cholestanol, and coprosterol, and that the sensitiveness of the vitamin D3 in the double compounds is considerably decreased. The vitamin D eflicacy, is preserved and corresponds to the vitamin D: content. The greater stability of the double compounds allows a more convenient handling of vitaminDa, so that a storage or use without special precautions is possible.

A further advantage of the new double compounds consists in that they show a good crystallizability. As the vitamin D3 also in nearly pure form is difllcult to crystallize, variable amounts and partly only very moderate yields of crystallized vitamin D3 are obtained. When, however, a double compound .with one of the above menis precipitated in nearly the theoretical yield in the crystallized state from solutions containing it.

The manufacture of the double compounds may be performed as follows:

tioned compounds is formed the vitamin D:

To a solution of vitamin D3, for instance in acetone, methanol, or alcohol, an equivalent amount of for instance cholesterol is added and the whole heated until the sterol is dissolved.

natural or synthetically prepared vitamin D: is

employed. The vitamin D: double compounds are stable and may be recrystallized unchanged from suited solvents.

The following examples illustrate the invention without, however, restricting it thereto.

Example 1 15 g. of vitamin D3 dinitrobenzoate are heated to boiling with 45 cc. of a 10 per cent methylalcoholic potassium lye for 10 minutes. After cooling the saponifled solution is diluted with double the volume of water and the free vitamin D3 extracted with ether. The ethereal extract is evaporated in vacuo after drying over sodium sulfate. The residue is dissolved in 150 cc. of acetone, mixed with 9.5 g. of cholesterol and heated to boiling until it dissolves. The still warm acetone solution is mixed with water until turbidity occurs. After standing for a short time precipitation of the double compound of vitamin D: with cholesterol begins. After about 5 hours the crystallisate is filtered oil, washed with methanol and dried on the air. It represents-ilne needles of the melting point of 118- 119. The yield is -95 per cent of theory. The double compound shows a specific rotary power of [a]n=+25.25 in acetone.

If instead or cholesterol cholestanol is used in the above example a double compound with similar properties is obtained having a melting point of 116 and showing a rotary power of -[a]=+55.5 in acetone.

Example 2 35 g. of an irradiation product of 7-dehydrocholesterol-freed from unchanged starting material-are dissolved in cc. of acetone, mixed with 12 g. of cholesterol and heated to boiling until the cholesterol is absolutely dissolved. On cooling the doublecompound of vitamin D; with cholesterol isprecipitated in fine needles, whichif desired--may be purified-by dissolving in hot acetone and adding water until the solution begins to turn cloudy. Melting point: 118-ll9 C.

I claim:

1. Vitamin D3 double compounds with a sterol selected from the group consisting of cholesterol, cholestanol, and coprosterol.

2. The vitamin D: double compound with cholesterol crystallizing in thin needles, showing a melting point of 118-119 and the specific rotary power [a]p=+25.5 in acetone.

' 3. The vitamin D: double compound with cholestanol melting at 116 and showing the specific rotary power [u]n=+55.5 in acetone.

O'I'I'O LINSERT. 

